| Autor: |
Sung-Gil Chi, Hyo-Jong Kim, Kil Yeon Lee, Sun Jin Park, Jikhyon Han, Nam-Goo Her, Tae-Kyu Ha, Byung-Kyu Ryu, Seong-In Jeong, Min-Goo Lee, Hye-Yeon Han, Min-Ju Kang, Jin-Hee Lee |
| Rok vydání: |
2023 |
| DOI: |
10.1158/1078-0432.c.6520779.v1 |
| Popis: |
Purpose:PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis.Experimental Design: Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-κB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays.Results: PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G1 cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFα, and its level correlated with tumor cell sensitivity to TNFα-induced apoptosis. PRKCDBP induction by TNFα was disrupted by blocking NF-κB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFα, and this response was abolished by disruption of a κB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFα-induced apoptosis.Conclusions:PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-κB in response to TNFα. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFα and other stresses, particularly under chronic inflammatory microenvironment. Clin Cancer Res; 17(24); 7551–62. ©2011 AACR. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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